Local thermal ablation breaks immune tolerance in pacreatic cancer [RNA-seq 1]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA884355 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21710700.fastq.gz | Fastqsanger.gz | |||
| SRR21710701.fastq.gz | Fastqsanger.gz | |||
| SRR21710702.fastq.gz | Fastqsanger.gz | |||
| SRR21710703.fastq.gz | Fastqsanger.gz | |||
| SRR21710704.fastq.gz | Fastqsanger.gz |
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Project description:Pancreatic cancer (PC) is a devastating disease characterised by late diagnosis, genetic neoplastic heterogeneity, poor T-cell infiltration, a highly immunosuppressive tumour microenvironment, and metastatic spreading which results in poor clinical outcomes. Surgery remains the most effective treatment, although it is limited to a few patients. Local ablative techniques, such as radiofrequency ablation (RFA), have been proposed to control PC progression in patients with nonresectable tumours. However, the impact of these therapies on promoting the activation of the immune system and eliciting an effective anti-tumour immune response remains elusive. Whether local ablative techniques could overcome resistance to immunotherapy in PC is unknown. We enrolled a cohort of patients with non-resectable locally advanced pancreatic cancer and longitudinally evaluated the impact of local thermal ablation on circulating immunological parameters. Additionally, we used cancer cell lines derived from PC transgenic mouse models to establish a preclinical platform that recapitulates systemic and localised inflammation induced by RFA in vivo. Finally, we employed this preclinical experimental platform to evaluate the efficacy of the therapeutic treatments. Thermal ablation induced a short-term inflammatory process resulting in a systemic increase in myeloid cells as well as increased plasma levels of high mobility group box 1 molecule, which correlates with a better patient outcome. We performed thermal ablative procedures in mice bearing orthotopic PC and evaluated the therapeutic efficacy of thermal treatment alone or in combination with immune checkpoint-based immunotherapy through activation of a T lymphocyte-dependent anti-tumour immune response. We demonstrated that RFA synergises with immunotherapy to restrict tumour progression, significantly improving the overall survival of PC-bearing mice. Tumour immune landscape characterisation confirmed that RFA in combination with immunotherapy supported the sculpting of an immune hostile milieu towards an effective anti-tumour milieu characterised by an increased infiltration of cytotoxic T lymphocytes in spite of CD206-expressing tumour-associated macrophages. Our study confirmed that RFA enhances immunotherapy effectiveness by breaking tumour immune tolerance and unleashing the full cytotoxic abilities of tumour-specific T-cells. Thus, RFA can circumvent the current limitations of immunotherapy in patients with pancreatic cancer.
2024-11-25 | GSE214202 | GEO
Project description:Pancreatic cancer (PC) is a devastating disease characterised by late diagnosis, genetic neoplastic heterogeneity, poor T-cell infiltration, a highly immunosuppressive tumour microenvironment, and metastatic spreading which results in poor clinical outcomes. Surgery remains the most effective treatment, although it is limited to a few patients. Local ablative techniques, such as radiofrequency ablation (RFA), have been proposed to control PC progression in patients with nonresectable tumours. However, the impact of these therapies on promoting the activation of the immune system and eliciting an effective anti-tumour immune response remains elusive. Whether local ablative techniques could overcome resistance to immunotherapy in PC is unknown. We enrolled a cohort of patients with non-resectable locally advanced pancreatic cancer and longitudinally evaluated the impact of local thermal ablation on circulating immunological parameters. Additionally, we used cancer cell lines derived from PC transgenic mouse models to establish a preclinical platform that recapitulates systemic and localised inflammation induced by RFA in vivo. Finally, we employed this preclinical experimental platform to evaluate the efficacy of the therapeutic treatments. Thermal ablation induced a short-term inflammatory process resulting in a systemic increase in myeloid cells as well as increased plasma levels of high mobility group box 1 molecule, which correlates with a better patient outcome. We performed thermal ablative procedures in mice bearing orthotopic PC and evaluated the therapeutic efficacy of thermal treatment alone or in combination with immune checkpoint-based immunotherapy through activation of a T lymphocyte-dependent anti-tumour immune response. We demonstrated that RFA synergises with immunotherapy to restrict tumour progression, significantly improving the overall survival of PC-bearing mice. Tumour immune landscape characterisation confirmed that RFA in combination with immunotherapy supported the sculpting of an immune hostile milieu towards an effective anti-tumour milieu characterised by an increased infiltration of cytotoxic T lymphocytes in spite of CD206-expressing tumour-associated macrophages. Our study confirmed that RFA enhances immunotherapy effectiveness by breaking tumour immune tolerance and unleashing the full cytotoxic abilities of tumour-specific T-cells. Thus, RFA can circumvent the current limitations of immunotherapy in patients with pancreatic cancer.
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Project description:Thermal history plays a role in the response of corals to subsequent heat stress. Prior heat stress can have a profound impact on later thermal tolerance, but the mechanism for this plasticity is not clear. The understanding of gene expression changes behind physiological acclimatization is critical in forecasts of coral health in impending climate change scenarios. Acropora millepora fragments were preconditioned to sublethal bleaching threshold stress for a period of 10 days; this prestress conferred bleaching resistance in subsequent thermal challenge, in which non-preconditioned coral bleached. Using microarrays, we analyze the transcriptomes of the coral host, comparing the bleaching-resistant preconditioned treatment to non-preconditioned and control treatments.
2012-11-29 | GSE41435 | GEO
Project description:Thermal history plays a role in the response of corals to subsequent heat stress. Prior heat stress can have a profound impact on later thermal tolerance, but the mechanism for this plasticity is not clear. The understanding of gene expression changes behind physiological acclimatization is critical in forecasts of coral health in impending climate change scenarios. Acropora millepora fragments were preconditioned to sublethal bleaching threshold stress for a period of 10 days; this prestress conferred bleaching resistance in subsequent thermal challenge, in which non-preconditioned coral bleached. Using microarrays, we analyze the transcriptomes of the coral host, comparing the bleaching-resistant preconditioned treatment to non-preconditioned and control treatments. This experiment compared host gene expression of Acropora millepora across control, non-preconditioned, and preconditioned treatments. Fragments were sampled prior to preconditioning (Day 4), following 10 days of thermal preconditioning (Day 20), and after two (Day 23), four (Day 25), and eight days (Day 29) of 31M-BM-0C thermal challenge. The analysis implements 45 arrays, representing 5 sampling points of three treatments (n=3).
2012-11-29 | E-GEOD-41435 | biostudies-arrayexpress
Project description:Local ablation disrupts immune evasion in pancreatic cancer
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Project description:The primary objective is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable colorectal liver metastases (≤3cm) and no extrahepatic disease.
| 2239386 | ecrin-mdr-crc
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Project description:Multiple articles report that thermal ablation is a safe and effective treatment for unresectable colorectal liver metastases (CRLM) ≤3cm. However efficacy of thermal ablation decreases with increasing lesion size. Guidelines state that thermal ablation is the preferred option for unresectable CRLM ≤3cm and stereotactic body radiotherapy (SBRT) when thermal ablation is not possible. It remains uncertain what local treatment method should be recommended for unresectable CRLM of 3-5cm.
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